EP0138849B1 - Process for the preparation of lineatin - Google Patents

Process for the preparation of lineatin Download PDF

Info

Publication number
EP0138849B1
EP0138849B1 EP84900899A EP84900899A EP0138849B1 EP 0138849 B1 EP0138849 B1 EP 0138849B1 EP 84900899 A EP84900899 A EP 84900899A EP 84900899 A EP84900899 A EP 84900899A EP 0138849 B1 EP0138849 B1 EP 0138849B1
Authority
EP
European Patent Office
Prior art keywords
formula
oxidation
subjected
derivative
trimethyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP84900899A
Other languages
German (de)
French (fr)
Other versions
EP0138849A1 (en
Inventor
Lars Institute of Chemistry SKATTEBÖL
Yngve Institute of Chemistry STENSTRÖM
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Borregaard Industries Ltd
Original Assignee
Borregaard Industries Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Borregaard Industries Ltd filed Critical Borregaard Industries Ltd
Priority to AT84900899T priority Critical patent/ATE33840T1/en
Publication of EP0138849A1 publication Critical patent/EP0138849A1/en
Application granted granted Critical
Publication of EP0138849B1 publication Critical patent/EP0138849B1/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
    • C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C07C45/292—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups with chromium derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
    • C07C47/21—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/203—Unsaturated compounds containing keto groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/647—Unsaturated compounds containing a keto groups being part of a ring having unsaturation outside the ring
    • C07C49/653—Unsaturated compounds containing a keto groups being part of a ring having unsaturation outside the ring polycyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/76—Benzo[c]pyrans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed systems

Definitions

  • lineatin is a pheromone which attracts certain species of ambrosia beetles (Trypodendron). This attraction is particularly strong when lineatin is used in admixture with certain other chemical substances, for instance as described in our Norwegian patent 144.029.
  • R 1 and R 2 may be hydrogen or lower alkyl.
  • a catalyst such as p-toluene sulfonic acid.
  • the preparation of the newcompound2 suitably takes place in a perse known manner (Bly etal, J. Am. Chem. Soc. 91 (1969) 3292) by reacting 1 with a suitable Grignard reagent, such as ⁇ -methyl allylmagnesium chloride.
  • the preparation of the new compound 3 also takes place in a per se known manner [Brown et a/, J. Am. Chem. Soc. 83 (1961) 2952 and J. Org. Chem., 36 (1971) 387] by oxidizing 2 with a mild oxidizing agent which oxidizes the secondary hydroxyl group to a keto group without attacking the double bond in 2.
  • Suitable oxidizing agents are for instance bichromate, Jones reagent and DMSO.
  • the oxidation is carried out with chromate or dichromate in an acidic medium.
  • reaction is a thermal intramolecular cycloaddition in which the reaction conditions are dependant upon several factors, including the groups R, and R 2 .
  • the reaction may be carried out by distilling the compound through a suitably heated tube under reduced pressure. Too high temperatures, such as above 550°C, may result in excessive amounts of other products such as 8 due to competing reactions, while too low temperatures, such as below 400°C, will result in incomplete reaction.
  • the reaction time may for instance be adjusted by varying the pressure when the compound-3 is distilled through a heated tube, since higher pressure will result in a longer residence time in the reactor.
  • the pressure is kept lower than 10 mm Hg. It is also possible to extend the residence time (reaction time) by using a longer reactor and/or increase the resistance therein.
  • the suitable temperature will be 470-510°C, preferably 480-500°C, in particular about 490°C.
  • Compound 4 is converted to the new compound 5 by simultaneous ring expansion of the cyclopentane ring and oxidation of the double bond by means of an organic peracid such as an optionally substituted perbenzoic acid or pertrifluoro acetic acid.
  • an organic peracid such as an optionally substituted perbenzoic acid or pertrifluoro acetic acid.
  • Compound 5 is converted to compound 6 by further oxidation using a periodate in an acidic medium.
  • the present process is clearly superior according to this comparison. There are of course other factors which are essential, such as the price of reagents and solvents used, methods of separation and difficulty in carrying out the operations.
  • the present process is in these respects most favourable. It is based on generally cheap reagents and ordinary solvents. The separation generally takes place by distillatiori. The total yield according to the present process is based on propargyl alcohol and isobutyraldehyde, which are both cheap chemicals.
  • 2,2-dimethyl-3,4-pentadienal (1a) was prepared according to US-patent 3,236,869 from propargyl alcohol and isobutyraldehyde in tetraline or 1,3-diisopropylbenzene with p-toluene sulphonic acid as catalyst. Yield 34 ⁇ 39%.
  • the product 1a was characterized by GC, NMR and IR. Bp. 131°C (lit. 131°C).
  • 2,2,5-trimethyl-3,4-hexadienal (1b) was prepared according to Bly et al (see above) from 2-methyl-3- butyn-2-ol, isobutyraldehyde, benzene and catalytic amounts of p-toluene sulphonic acid. Distillation gave a yield of 50% (lit. 38%).
  • the product 1b was characterized by GC (>98% pure), NMR and IR. Bp. 103°C/100 mm Hg (lit. 96-9 0 C/104 mm Hg).
  • 2,5,5,8-tetramethylnona-1,6,7-trien-4-ol (2b) was prepared as described for 2a from 8.72 g (0.36 mole) of Mg, 32.65 g (0.36 mole) of ⁇ -methylallyl chloride and 16.61 g (0.12 mole) of 1b. The work up resulted in 21.44 g (92%) of 2b.. Bp. 61 ⁇ 2°C/0.3 mm Hg, n D 16 1.4810.
  • the ketolactone 6 (3.20 g, 17.6 mmoles) was suspended in 70 ml of dry ether and cooled to -60°C. 39 ml of 1.0 M (39 mmoles) diisobutylaluminium hydride in hexane were added dropwise with stirring. The temperature of the solution was kept between -70 and -60°C. The solution was stirred at this temperature for about 2 hours. 64 ml of saturated NH 4 CI solution were slowly added dropwise before the solution was heated to 0°C, and it was then acidified with 46 ml of 4N HCI. The solution was further stirred for 1.5 hours.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

New process for preparing the pheromone active compound lineatin (3,3,7-trimethyl-2,9-dioxatricyclo AD3,3,1,04,7 BD-nonane), by reacting a 2,2-dimethyl-3,4-pentadienal of formula (1), in which R1 and R2 is each hydrogen or lower alkyl, with beta-methylallyl magnesium halide; the formed 2,5,5-trimethylocta-1,6,7-trien-4-ol derivative of formula (2) is subjected to oxidation which does not attack the double bonds; the formed 2,5,5-trimethylocta-1,6,7-trien-4-one derivative of formula (3) is subjected to pyrolysis; the formed 1,4,4-trimethyl-6-methylenebicyclo AD3,2,0 BDheptan-3-one derivative of formula (4) is subjected to oxidation; the resulting 5,5,9-trimethyl-2,6-dioxa-7-oxo-bicyclo AD4,2,0 BDoctylspiro AD2,7 BD-decane derivative of formula (5) is subjected to oxidation; the resulting 1,5,5-trimethyl-4-oxabicyclo AD4,2,0 BD-octan-3,7-dione of formula (6) is reduced in a per se known manner to lineatin of formula (7). Compounds (2), (3), (4) and (5) are novel.

Description

  • It is known that lineatin is a pheromone which attracts certain species of ambrosia beetles (Trypodendron). This attraction is particularly strong when lineatin is used in admixture with certain other chemical substances, for instance as described in our Norwegian patent 144.029.
  • There are described several processes for the preparation of lineatin, and the following may be mentioned:
    • A. Borden, J. H.; Handley, J. R.; Johnston, B. D.; MacConnell, J. G.; Silverstein, R. M.; Slessor, K. N.; Swigar, A. A. and Wong, D. T. W. J. Chem. Ecol. 5 (1979) 681.
    • B. Mori, K. and Sasaki, M. Tetrahedron Lett. (1979) 1329.
    • C. Idem. Tetrahedron 36 (1980) 2197.
    • D. Slessor, K. N.; Oehlschlager, A. C.; Johnston, B. D.; Pierce, H. D. Jr.; Grewal, S. K. and Wickremesinghe, L. K. G. J. Org. Chem. 45 (1980) 2290.
    • E. KcKay, W.; Ounsworth, J.; Sum, P.-E. and Weiler, L, Can. J. Chem. 60 (1982) 872.
    • F. Mori., K.; Uematsu, T.; Minobe, M. and Yanagi, K. Tetrahedron Lett. 23 (1982) 1921.
    • G. White, J. D., Avery, M. A. and Carter, J. P. J. Am. Chem. Soc. 104 (1982) 5486. None of these known processes can be considered as satisfactory with respect to yield, economy and simple operation. Thus, several are carried out by using photochemical reactions, which may easily give rise to considerable problems, particularly when carried out in large scale.
  • According to the invention there has been found a new process which leads to the desired lineatin with satisfactory yield by using commercially available cheap reagents and solvents, without using photochemical reactions.
  • The process according to the invention may be illustrated as follows:
    Figure imgb0001
    R1 and R2 may be hydrogen or lower alkyl. The examples illustrate R1=R2=H (a) and R,=R2=CH3 (b).
  • The preparation of 1 may be carried out in a perse known manner (US-patent 3,236,869) by reacting isobutyraldehyde with propargylalcohol (R,=R2=H) or a suitable derivative thereof in the presence of a catalyst such as p-toluene sulfonic acid.
    • Step i
  • The preparation of the newcompound2 suitably takes place in a perse known manner (Bly etal, J. Am. Chem. Soc. 91 (1969) 3292) by reacting 1 with a suitable Grignard reagent, such as β-methyl allylmagnesium chloride.
    • Step ii
  • The preparation of the new compound 3 also takes place in a per se known manner [Brown et a/, J. Am. Chem. Soc. 83 (1961) 2952 and J. Org. Chem., 36 (1971) 387] by oxidizing 2 with a mild oxidizing agent which oxidizes the secondary hydroxyl group to a keto group without attacking the double bond in 2. Suitable oxidizing agents are for instance bichromate, Jones reagent and DMSO. Preferably the oxidation is carried out with chromate or dichromate in an acidic medium.
    • Step iii
  • The preparation of the new compound 4 from 3 is an important feature of the invention.
  • Here the reaction is a thermal intramolecular cycloaddition in which the reaction conditions are dependant upon several factors, including the groups R, and R2. In order to attain complete reaction it is necessary that the compound 3 is kept for some time at a specific temperature. In practice the reaction may be carried out by distilling the compound through a suitably heated tube under reduced pressure. Too high temperatures, such as above 550°C, may result in excessive amounts of other products such as 8 due to competing reactions, while too low temperatures, such as below 400°C, will result in incomplete reaction. The lower the reaction temperature is, the longer the reaction time must be. The reaction time may for instance be adjusted by varying the pressure when the compound-3 is distilled through a heated tube, since higher pressure will result in a longer residence time in the reactor. Normally the pressure is kept lower than 10 mm Hg. It is also possible to extend the residence time (reaction time) by using a longer reactor and/or increase the resistance therein. In general and for instance when R,=R2=H and the length and the diameter of the tube are 60 cm and 2.5 cm respectively, and it is packed with silica wool, the suitable temperature will be 470-510°C, preferably 480-500°C, in particular about 490°C.
    • Step iv
  • Compound 4 is converted to the new compound 5 by simultaneous ring expansion of the cyclopentane ring and oxidation of the double bond by means of an organic peracid such as an optionally substituted perbenzoic acid or pertrifluoro acetic acid.
    • Step v
  • Compound 5 is converted to compound 6 by further oxidation using a periodate in an acidic medium.
    • Step vi
  • The conversion of compound 6 to lineatin 7 takes place in a known manner by reduction, for instance as described in E above with diisobutyl aluminium hydride.
  • Among the previously suggested syntheses of lineatin only six may be compared with the present process, since Borden et al (A) does not give any yield or experimental details for the synthesis.
  • In the following a comparison has been made between the syntheses by considering a) number of steps, b) percent total yield from commercially available starting materials and c) photochemical step. The latter has been included since it may present great problems to carry out photochemical reactions in a larger scale as mentioned above. They also require special equipment.
    Figure imgb0002
  • The present process is clearly superior according to this comparison. There are of course other factors which are essential, such as the price of reagents and solvents used, methods of separation and difficulty in carrying out the operations. The present process is in these respects most favourable. It is based on generally cheap reagents and ordinary solvents. The separation generally takes place by distillatiori. The total yield according to the present process is based on propargyl alcohol and isobutyraldehyde, which are both cheap chemicals.
  • Examples of the individual process steps are given below.
  • Unless otherwise is mentioned, the NMR spectra have been recorded on a Varian 60 MHz instrument.
    • Example 1
  • 2,2-dimethyl-3,4-pentadienal (1a) was prepared according to US-patent 3,236,869 from propargyl alcohol and isobutyraldehyde in tetraline or 1,3-diisopropylbenzene with p-toluene sulphonic acid as catalyst. Yield 34―39%. The product 1a was characterized by GC, NMR and IR. Bp. 131°C (lit. 131°C).
    • Example 2
  • 2,2,5-trimethyl-3,4-hexadienal (1b) was prepared according to Bly et al (see above) from 2-methyl-3- butyn-2-ol, isobutyraldehyde, benzene and catalytic amounts of p-toluene sulphonic acid. Distillation gave a yield of 50% (lit. 38%). The product 1b was characterized by GC (>98% pure), NMR and IR. Bp. 103°C/100 mm Hg (lit. 96-90C/104 mm Hg).
    • Example 3
  • 2,5,5-trimethylocta-1,6,7-trien-4-ol (2a). 300 ml of absolute ether were added to 7.29 g (0.30 mole) of dry Mg, the mixture was cooled to 15 ± 1°C, and 27.19 g (0.30 mole) freshly distilled β-methylallyl chloride were added. The mixture was stirred overnight at the same temperature. The white suspension was cooled to 0°C, and 11.03 g (0.10 mole) la in 150 ml absolute ether were added dropwise during 1 hour. The mixture was stirred at 0°C for 4 hours (reaction monitored on GC). 37 ml of saturated NH4CI solution were added with vigorous stirring. The solution was decanted from the magnesium salts which were washed several times with ether. The combined ether phases were dried (MgS04). Distillation gave 14.22 g (91 %) 2a, b.p. 60-1°C/1.5 mm Hg.
  • IR (film): 3580 (m), 3490 (m), 3085 (m), 2980 (s), 2945 (s), 2885 (m), 1960 (s), 1653 (m), 1465 (m), 1395 (m), 1382 (m), 1300 (m), 1270 (m), 1180 (m), 1068 (s), 997 (m), 893 (s), 847 (s), 645 (w) cm-1. 1H NMR (CCl4) 5 1.02 (s, 6H), 1.53 (bs, 1H), 1.73 (bs, 3H), 1.88-2.22 (m, 2H), 3.30 (dd, J1 3Hz, J2 10Hz, 1 H), 4.56―5.23 (m, 5H).
    • Example 4
  • 2,5,5,8-tetramethylnona-1,6,7-trien-4-ol (2b) was prepared as described for 2a from 8.72 g (0.36 mole) of Mg, 32.65 g (0.36 mole) of β-methylallyl chloride and 16.61 g (0.12 mole) of 1b. The work up resulted in 21.44 g (92%) of 2b.. Bp. 61―2°C/0.3 mm Hg, nD 16 1.4810.
  • IR (film): 3474 (s), 3070 (m), 2960 (s), 2860 (s), 2705 (w), 1966 (m), 1642 (m), 1437 (s), 1361 (s), 1287 (m), 1183 (m), 1058 (s), 1010 (m), 884 (s), 806 (m) cm-1. 1H NMR (CCl4): δ 0.95 (s, 6H), 1.50―2.43 (m, 11H), 2.98 (bs, 1H), 3.28 (dd, J1 3Hz, J2 10Hz,, 1 H), 4.67-5.00 (m, 3H).
    • Example 5
  • 2,5,5-trimethylocta-1,6,7-trien-4-one (3a). Brown's oxidation method (see Brown et al above) was used. The oxidizing reagent was prepared as described in the literature. 35.20 g (0.21 mole) of 2a were dissolved in a 100 ml of ether, and with vigorous stirring the oxidation reagent was added very slowly until the alcohol had reacted according to GC (about 4 days). 355 ml of the reagent (corresponding to 0.234 mole of Na2Cr2O7) had then been added.
  • The organic phase was separated, and the aqueous phase was extracted with ether (3 x 75 mi). The combined organic phases were extracted with saturated NaHC03 (1 x 75 ml) and water (1 x 50 ml), dried (MgS04), evaporated and distilled. The yield was 30.90 g (90%) of 3a.
  • Jones oxidation was carried out on 2a. A large excess of the oxidizing agent had to be added for complete reaction, which resulted in a more difficult work up than by Brown's method and which also gave a poorer yield (78%). 3a, b.p. 63-5°C/3.5 mm Hg.
  • IR (film): 3085 (m), 2980 (s), 2940 (s), 1957 (s), 1715 (s), 1653 (m), 1467 (m), 1391 (m), 1370 (m), 1325 (m), 1225 (w), 1153 (w), 1060 (m), 1035 (m), 1003 (w), 892 (s), 847 (s), 787 (w) cm-1. 1H NMR (CDCl4): 6 1.23 (s, 6H), 1.72 (bs, 3H), 3.23 (s, 2H), 4.63-5.33 (m, 5H).
  • The 2,4-dinitrophenylhydrazone of 3a (recrystallized from ethanol), m.p. 63-4°C.
    • Example 6
  • 2,5,5,8-tetramethylnona-1,6,7-trien-4-one (3b), was prepared as described for 3a from 10.00 g (51,5 mmole) of 2b. Work up as above gave 8.9 g (90%) of 3b, bp. 70-2°C/0.5 mm Hg, nD 16 1.4754.
  • IR (film): 3073 (m), 2966 (s), 1961 (w), 1778 (w), 1702 (s), 1647 (m), 1442 (s), 1361 (s), 1314 (s), 1239 (m), 1187 (m), 1055 (s), 1011 (m), 967 (w), 942 (w), 885 (s), 837 (w), 801 (m) cm-1. 1H NMR (CCl4: δ 1.17 (s, 6H), 1.70 (s, 6H), 1.73 (s, 3H), 3.14 (s, 2H), 4.57-5.03 (m, 3H).
    • Example 7
  • 1,4,4-trimethyl-6-methylenebicyclo[3.2.0]heptan-3-one (4a). 5.00 g (32.4 mmole) of 3a were distilled through a 60 cm long quartz tube packed with 14 g of silica wool and heated to 490 ± 5°C at 0.5 mm Hg. The reaction was monitored by allene absorption on IR. After distillation twice all the allene had reacted. Two products 4a and 8 of 60 and 20% percent respectively, dominated the mixture which was distilled through a good column (Fischer Spaltrohr, 60 theoretical bottoms). 41.4 g of a 5% (w/w) ethanolic (96%) AgNO3 solution were added to the distillate, and after some hours 8 had been precipitated as the silver acetylide (9) (not shown). It was filtered off and air dried. The filtrate was concentrated by distillation at atmospheric pressure. Distillation gave 2.31 g (46%) of 4a, bp. 69-70°C (4 mm Hg), mp -23 to -20°C. Analysis:
    • Calculated for C11H16O: C 80.44, H 9.82
    • Found: C 79.69, H 9.60%.
  • 4a: IR (film): 3085 (w), 2970 (s), 2875 (m), 1743 (s), 1718 (m), 1675 (m), 1460 (m), 1382 (m), 1095 (m), 882 (m) cm-1. 1H NMR (CDCI3, 400 mHz), 5 1.08 (s, 3H), 1.09 (s, 3H), 1.43 (s, 3H), 2.28 (d, J 18Hz, 1H), 2.37 (dq, J1 14Hz, J2 2.8Hz, 1 H), 2.57 (2s, J1 18Hz, J2 14Hz, 2H), 2.79 (q, J 2.8Hz, 1 H), 4.88 (q, J1 2.8Hz, J2 4Hz, 1 H), 4.92 (q, J1 2.8Hz, J2 4Hz, 1H). 13C NMR (CDCl3 50.3 MHz): δ 19.1 (CH3), 27.1 (CH3), 27.9 (CH3), 34.4
    Figure imgb0003
    61.6 (-C-H), 111.5 (CH2=), 144.7 (>C=), 221.8 (>C=O). Mp. for the 2,4-dinitrophenylhydrazone of 4a: 119-120°C.
  • 2.68 g (6.1 mmoles) of 9 were added to 0.75 g (15.3 mmoles) of NaCN in 5 ml of water, refluxed for 4 hours until all had been dissolved, cooled, extracted with ether, dried (MgS04) and evaporated. This gave 0.92 g of pure 8 while at the same time the silver was recovered. 8: M.p. 61-62°C, Bp. 69-70°C/4 mm Hg.
  • IR (CDCI3): 3315 (s), 2970 (s), 2940 (m), 2885 (m), 2125 (w), 1743 (s), 1468 (m), 1412 (w), 1385 (m), 1375 (m), 1235 (m) cm-1.
  • 'H NMR (CDCI3): 1.13 (s, 3H), 1.15 (s, 3H), 1.20 (s, 3H), 1.25 (s, 3H), 2.25 (s, 2H), 2.27 (d, J 3Hz, 1H), 2.68 (d, J 3Hz, 1 H).
  • '3C NMR (CDCI3, 50.3 MHz) δ 22.8 (CH3), 24.4 (CH3), 27.5 (CH3), 29.5 (CH3), 37.1 (C-4, >C<), 47.9 (C-2, >C<), 51.6 (CH) and 52.1 (CH2), 74.0 (=C-H), 80.6 (-C=), 221.2 (C=O).
    • Example 8
  • 6-isopropylidene-1,4,4-trimethylbicyclo[3.2.0]heptan-3-one (4b). 5.00 g (26.0 mmoles) of 3b were distilled through the same column as used for 3a. The reaction was monitored on GC. The main product 4b was separated by distillation on a good column (Fischer Spalt rohr, 60 theoretical plates) with >97% purity. The yield was 2.55 g (51%). Bp. 68°C/0.2 mm Hg.
  • IR (film): 2920 (s), 2861 (s), 2824 (m), 2721 (w), 1735 (s), 1449 (s), 1409 (m), 1376 (s), 1359 (m), 1303 (m), 1286 (m), 2141 (m), 1206 (m), 1158 (w), 1120 (s), 1085 (m), 1055 (m), 1042 (m), 911 (m), 898 (m), 868 (w), 707 (w) cm-1.
  • 1H NMR (CDCI3): 1.00 (s, 3H), 1.10 (s, 3H), 1.37 (s, 3H), 1.50 (b s, 6H), 2.28 (b s, 3H), 2.40 (b s, 1H), 2.73 (b s,1H).
    • Example 9
  • 5,5,9-trimethyl-2,6-dioxa-7-oxobicyclo[4.2.0]octylspiro[2,7]decane (5a). 2.96 g (18.0 mmoles) of 4a were dissolved in 40 ml of dry CH2Cl2. 8.05 g 81% (corresponding to 6.52 g and 37.8 mmoles) of m-chloroperbenzoic acid (m-CPBA) and 3.86 g (46.0 mmoles) of NaHC03 were mixed and added to the above solution. The mixture was stirred overnight at room temperature, and 35 ml of 10% Na2S203 were then added. After half an hour's stirring, the organic phase was separated, and the aqueous phase was extracted with CH2CI2 (2 x 20 ml). The combined organic phases were washed with a saturated NaHC03 solution (1 x 20 ml) and saturated NaCl solution (1 x 20 ml), dried (MgS04) and evaporated. The crude product weighed 3.58 g (100%) and was pure according to GC. It was used for the next reaction without further purification.
  • 5a: 1H NMR (CDCI3, 98 MHz): 6 1.27 (s, 3H), 1.40 (s, 3H), 1.45 (s, 3H), 2.15 (d, J 13Hz, 1H), 2.36 (d, J 13Hz, 1 H), 2.56―2.81 (m, 4H), 3.42 (d, J 4Hz, 1 H). MS (Cl, isobutane) m/z 197 (M+ + 1).
    • Example 10
  • 3,3,5,5,9-pentamethyl 2,6-dioxa-7-oxobicyclo[4.2.0]octylspiro[2.7]decane (5b) was prepared in the same manner as described for 5a from 0.5 g (2.60 mmoles) of 4b, 1.16 g of 81 % (corresponding to 0.94 g and 5.46 mmoles) m-CPBA and 0.54 g (6.37 mmoles) of NaHC03. Work up as above gave 0.59 g (100%) of the crude product which was pure (GC) and was used directly further.
    • Example 11
  • 1,5,5-trimethyl-4-oxobicyclo[4.2.0]octan-3,6-dione (6)
    • i) From 5a. To a solution of 3.53 g (18 mmoles) 5a in 30 ml of absolute ether, 4.10 g (18 mmoles) of H5106 were added with vigorous stirring. The mixture was stirred overnight, and 5 ml of water were added. The ether phase was separated, and the aqueous phase was extracted with ether (2 x 15 ml). The combined ether phases were extracted with saturated Na2CO3 solution (1 x 20 ml) and saturated NaCl solution (1 x 20 ml), dried (MgS04) and evaporated. The crude product is 3.29 g (100%) of a crystalline compound (mp. 99-100°C) which has the same IR, NMR and MS data as given in the literature (C).
    • ii) From 5b. To a solution of 0.59 g (2.60 mmoles) crude 5b in 5 ml ether 0.60 g (2.60 mmoles) H5lO6 were added in the same manner and worked up as above. The product consisted of 6 and two other compounds. Recrystallization from 6-butyl methyl ether afforded 0.33 g (70%) of 6.
    Example 12 (±) lineatin (7).
  • The ketolactone 6 (3.20 g, 17.6 mmoles) was suspended in 70 ml of dry ether and cooled to -60°C. 39 ml of 1.0 M (39 mmoles) diisobutylaluminium hydride in hexane were added dropwise with stirring. The temperature of the solution was kept between -70 and -60°C. The solution was stirred at this temperature for about 2 hours. 64 ml of saturated NH4CI solution were slowly added dropwise before the solution was heated to 0°C, and it was then acidified with 46 ml of 4N HCI. The solution was further stirred for 1.5 hours. Extraction with ether (4 x 60 ml), washing of the combined ether phases with a saturated NaHC03 solution (1 x 60 ml), drying (MgS04) and evaporation at moderate vacuum (the temperature in the bath was <35°C) resulted in a crude product which upon distillation (bp. 60-62°C/3 mm Hg) gave 2.17 g of 7 (74%). The spectroscopic data were in agreement with those of the literature.
    • Example 13 (±) lineatin (7).
  • LiAl(OBut)3H-reduction of 6. To a stirred solution of 3.99 g (21.9 mmoles) 6 in 300 ml abs. ether at room temperature, 11.4 g (44.9 mmoles) LiAI(OBut)3H were added portion-wise during h. The suspension was stirred overnight and then 60 ml of 4M aqueous HCI were added. The solution was stirred for further 1.5 h. Extraction with ether (3 x 60 ml), washing of the combined ether phases with saturated NaHC03 (1 x 60 ml), drying (MgS04), and careful distillation gave 1.90 g (52%) 7, b.p. 60-2°C/3 mm Hg.

Claims (7)

1. Process for the preparation of lineatin (3,3,7-trimethyl-2,9-dioxatricyclo[3,3,1,04,7]nonane) of the formula
Figure imgb0013
characterized in that
i) a 2,2-dimethyl-3,4-pentadienal of the formula
Figure imgb0014
in which R1 and R2 each is hydrogen or lower alkyl, is reacted with β-methylallyl magnesiumhalide,
ii) the formed 2,5,5-trimethylocta-1,6,7-trien-4-ol derivative of the formula
Figure imgb0015
is subjected to oxidation which does not attack the double bonds,
iii) the formed 2,5,5-trimethylocta-1,6,7-trien-4-one derivative of the formula
Figure imgb0016
is subjected to pyrolysis at 400 to 550°C.
iv) the formed 1,4,4-trimethyl-6-methylene-bicyclo[3,2,0]heptan-3-one derivative of the formula
Figure imgb0017
is subjected to oxidation with an organic peracid,
v) the resulting 5,5,9-trimethyf-2,6-dioxa-7-oxobicycl[4,2,0]octylspiro[2,7]decane derivative of the formula
Figure imgb0018
is subjected to oxidation with a periodate in an acid medium,
vi) the resulting 1,5,5-trimethyl-4-oxabicyclo[4,2,0]octan-3,7-dione of the formula
Figure imgb0019
is reduced to lineatin in a manner known per se.
2. A process according to claim 1, wherein the oxidation of step ii) is carried out with chromate or dichromate in an acidic medium.
3. A process according to claim 1 or claim 2, wherein the pyrolysis of step iii) is carried out at 470 to 510°C.
4. A process according to claim 3, wherein the pyrolysis of step iv) is carried out at 480 to 500°C.
5. A process according to any preceding claim, wherein R1 and R2 are the same and are hydrogen or methyl.
EP84900899A 1983-03-15 1984-02-27 Process for the preparation of lineatin Expired EP0138849B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT84900899T ATE33840T1 (en) 1983-03-15 1984-02-27 MANUFACTURING PROCESS FOR LINEATIN.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NO830902A NO151935C (en) 1983-03-15 1983-03-15 PROCEDURE FOR PRODUCING LINEATIN.
NO830902 1983-03-15

Publications (2)

Publication Number Publication Date
EP0138849A1 EP0138849A1 (en) 1985-05-02
EP0138849B1 true EP0138849B1 (en) 1988-04-27

Family

ID=19886999

Family Applications (1)

Application Number Title Priority Date Filing Date
EP84900899A Expired EP0138849B1 (en) 1983-03-15 1984-02-27 Process for the preparation of lineatin

Country Status (13)

Country Link
US (1) US4578484A (en)
EP (1) EP0138849B1 (en)
JP (1) JPS60500863A (en)
CA (1) CA1198441A (en)
CS (1) CS244807B2 (en)
DD (1) DD219487A5 (en)
DE (1) DE3470746D1 (en)
FI (1) FI78914C (en)
NO (1) NO151935C (en)
PL (1) PL143243B1 (en)
SU (1) SU1366061A3 (en)
WO (1) WO1984003703A1 (en)
YU (1) YU43571B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8062651B1 (en) * 2004-03-16 2011-11-22 The United States Of America As Represented By The Secretary Of Agriculture Attractant pheromone for the male pink hibiscus mealybug, Maconellicoccus hirsutus (Green) (Homoptera: Pseudococcidae)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS55136284A (en) * 1979-04-06 1980-10-23 Sumitomo Chem Co Ltd Preparation of insect pheromone
JPS55139382A (en) * 1979-04-13 1980-10-31 Sumitomo Chem Co Ltd Production of insect pheromone

Also Published As

Publication number Publication date
CA1198441A (en) 1985-12-24
WO1984003703A1 (en) 1984-09-27
FI844309A0 (en) 1984-11-02
PL246667A1 (en) 1985-03-12
SU1366061A3 (en) 1988-01-07
FI78914C (en) 1989-10-10
EP0138849A1 (en) 1985-05-02
JPH0371432B2 (en) 1991-11-13
YU44884A (en) 1986-10-31
FI78914B (en) 1989-06-30
FI844309L (en) 1984-11-02
YU43571B (en) 1989-08-31
NO151935C (en) 1985-07-03
DD219487A5 (en) 1985-03-06
PL143243B1 (en) 1988-01-30
JPS60500863A (en) 1985-06-06
US4578484A (en) 1986-03-25
NO151935B (en) 1985-03-25
DE3470746D1 (en) 1988-06-01
NO830902L (en) 1984-09-17
CS244807B2 (en) 1986-08-14

Similar Documents

Publication Publication Date Title
US4371711A (en) Process for producing 4-hydroxycyclopentenones
US4097531A (en) Substituted cyclopropane process and product
EP0138849B1 (en) Process for the preparation of lineatin
US4181683A (en) 1,7-Octadien-3-one and process for preparing the same
US4517382A (en) 1-Formyl-tri- and tetramethyl-cyclohex-1-en-3-one oximes
US3624105A (en) Method for synthesizing rhodoxanthin
US4341897A (en) Pyranic derivatives for use in the preparation of muscone
US3845076A (en) Method of preparing aldehydes
Elsner et al. 121. Synthesis of cyclic hydrocarbons. Part IV. Alkylindanes
US3331856A (en) Method of preparing transhexahydroindanones
JPH0358335B2 (en)
US4431827A (en) Pentadecanolide derivatives
JPS6289660A (en) Production of 4-oxo-4,5,6,7-tetrahydroindole
JPH0753681B2 (en) Method for producing tropone derivative
EP0032712B1 (en) New process for preparing unsaturated bicyclic hydrocarbons
EP0062772A2 (en) Regioselective preparation of triazolylvinyl ketones and the intermediates therefor
US6278027B1 (en) 3-Substituted-2-halocycloheptenone compounds and a method for manufacturing same
HU200582B (en) New process for producing dihydroxyacyl benzenes as intermediate products of leukotriene antagonists
US3962281A (en) Method of preparing aldehydes
HU193454B (en) Process for producing 3-phenyl-butyraldehyde derivatives
SU1567565A1 (en) Method of obtaining 1-chlor-4-methylpentan 2-ol
SU827478A1 (en) Method of preparing 13-ketobicyclo/10,3,0/pentadec-1
JPH0597758A (en) Production of alpha,beta-unsaturated carbonyl compound
JP2002212149A (en) METHOD FOR PRODUCING TETRAALKYLAMMONIUM FLUORIDE AND METHOD FOR PRODUCING beta-HYDROXYKETONE BY USING THE SAME
JPH07126260A (en) 2-alkyl-3-styryloxiranecarboxylic acid ester and its production

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19841105

AK Designated contracting states

Designated state(s): AT BE CH DE FR GB LI LU NL SE

17Q First examination report despatched

Effective date: 19860203

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH DE FR GB LI LU NL SE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Effective date: 19880427

Ref country code: BE

Effective date: 19880427

REF Corresponds to:

Ref document number: 33840

Country of ref document: AT

Date of ref document: 19880515

Kind code of ref document: T

REF Corresponds to:

Ref document number: 3470746

Country of ref document: DE

Date of ref document: 19880601

ET Fr: translation filed
NLV1 Nl: lapsed or annulled due to failure to fulfill the requirements of art. 29p and 29m of the patents act
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Effective date: 19890227

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19890228

26N No opposition filed
GBPC Gb: european patent ceased through non-payment of renewal fee
PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 19900212

Year of fee payment: 7

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Effective date: 19910228

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 19940128

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: AT

Payment date: 19940210

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 19940222

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 19940307

Year of fee payment: 11

EUG Se: european patent has lapsed

Ref document number: 84900899.0

Effective date: 19911008

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Effective date: 19950227

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Effective date: 19950228

Ref country code: CH

Effective date: 19950228

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Effective date: 19951031

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Effective date: 19951101

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST